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  • Title: Signal transducers and activators of transcription (STATs) gene polymorphisms related with susceptibility to rheumatic heart disease in north Indian population.
    Author: Gupta U, Mir SS, Srivastava A, Garg N, Agarwal SK, Pande S, Mittal B.
    Journal: Immunol Lett; 2014 Sep; 161(1):100-5. PubMed ID: 24797343.
    Abstract:
    Rheumatic heart disease (RHD) is the most serious complication of heart that comprises inflammatory reactions in heart valves. Cytokines play a critical role in triggering inflammatory reactions and they activate the Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) signaling pathway. Altered signals of STATs play important roles in the balance between proinflammatory and anti-inflammatory cytokines in inflammatory diseases. The aim of the present study was to investigate for the association of polymorphisms related with STAT genes, i.e. STAT3 (rs4796793 C/G) and STAT5b (rs6503691 C/T) with the pathogenesis of RHD. This case-control association study involved 300 healthy controls and 400 RHD patients from North Indian Population. We categorized RHD patients into two subgroups based on involvement of heart valves, mitral valve lesion alone (MVL), and combined valve lesions including mitral valve (CVL). Genotyping was done by RFLP/Taqman probes. We observed that STAT3 CG and GG genotypes were significantly associated with RHD (p=0.030 and p=0.014 respectively), STAT5b CT and TT genotypes were also significantly associated with RHD (p≤0.001). Haplotype analysis revealed that minor alleles of both the variants (Grs4796793Trs6503691) were significantly associated (p<0.0001) with increased risk of the disease susceptibility irrespective of gender or age of onset of the disease. However, the polymorphisms were not involved in severity of RHD as both MVL and CVL patients were equally affected. STAT Grs4796793Trs6503691 carriers may have reduced production of STAT3 leading to damage of heart valves. Thus, STAT genes polymorphisms may be useful markers for the identification of individuals with high risk of RHD in the susceptible population.
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